Stem Cell ReportsPub Date : 2025-08-12Epub Date: 2025-07-17DOI: 10.1016/j.stemcr.2025.102577
Kaoru Takasaki, Eric K Wafula, Jian Meng Fan, Ying Ting Sit, Sara S Kumar, David Smith, Alyssa Gagne, Peter A Gearhart, Deborah L French, Christopher S Thom, Stella T Chou
{"title":"Single-cell transcriptomics reveal individual and cooperative effects of trisomy 21 and GATA1s on hematopoiesis.","authors":"Kaoru Takasaki, Eric K Wafula, Jian Meng Fan, Ying Ting Sit, Sara S Kumar, David Smith, Alyssa Gagne, Peter A Gearhart, Deborah L French, Christopher S Thom, Stella T Chou","doi":"10.1016/j.stemcr.2025.102577","DOIUrl":"10.1016/j.stemcr.2025.102577","url":null,"abstract":"<p><p>Trisomy 21 (T21) is associated with baseline erythrocytosis, thrombocytopenia, neutrophilia, transient abnormal myelopoiesis (TAM), and myeloid leukemia of Down syndrome (ML-DS). TAM and ML-DS blasts harbor mutations in GATA1, resulting in the exclusive expression of the truncated isoform GATA1s. Germline GATA1s mutations in individuals without T21 cause congenital cytopenias, typically without a leukemic predisposition. To dissect the developmental effects of T21 and GATA1s, we used a combination of isogenic human induced pluripotent stem cells, primary human fetal and neonatal cells, and single-cell transcriptomics to interrogate hematopoietic progenitors differing only by chromosome 21 and/or GATA1 status. Both T21 and GATA1s induced early lineage skewing, and trajectory analysis revealed that GATA1s altered the temporal regulation of lineage-specific transcriptional programs, disrupting cell proliferation and maturation irrespective of chromosomal context. These studies uncovered unexpected heterogeneity and lineage priming in early, multipotent hematopoietic progenitors and identified transcriptional and functional maturation blocks linked to GATA1s.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102577"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-08-12Epub Date: 2025-07-03DOI: 10.1016/j.stemcr.2025.102576
Colin Trepicchio, Gat Rauner, Nicole Traugh, Ruohong Wang, Meadow Parrish, Daniel E C Fein, Youssof Mal, Piyush B Gupta, Stefano Monti, Charlotte Kuperwasser
{"title":"DDR1 regulates RUNX1-CBFβ to control breast stem cell differentiation.","authors":"Colin Trepicchio, Gat Rauner, Nicole Traugh, Ruohong Wang, Meadow Parrish, Daniel E C Fein, Youssof Mal, Piyush B Gupta, Stefano Monti, Charlotte Kuperwasser","doi":"10.1016/j.stemcr.2025.102576","DOIUrl":"10.1016/j.stemcr.2025.102576","url":null,"abstract":"<p><p>Understanding epithelial stem cell differentiation and morphogenesis during breast tissue development is essential, as disruption in these processes underlie breast cancer formation. We used a next-generation single-cell-derived organoid model to investigate how individual stem cells give rise to complex tissue. We show that discoidin domain receptor 1 (DDR1) inhibition traps cells in a bipotent state, blocking alveolar morphogenesis and luminal cell expansion, which is necessary for complex epithelium formation. Disrupting RUNX1 function produced nearly identical phenotypes, underscoring its critical role downstream of DDR1. Mechanistically, DDR1 affects the interaction and expression of RUNX1 and its cofactor core binding factor beta (CBFβ), thereby regulating its activity. Mutational analyses in breast cancer patients reveal frequent alterations in the DDR1-RUNX1 signaling axis, particularly co-occurring mutations. Together, these findings uncover DDR1-RUNX1 as a central signaling pathway driving breast epithelial differentiation, whose dysregulation may contribute fundamentally to breast cancer pathogenesis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102576"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Transcription factor-mediated germ cell induction in rats reveals ETV4 cooperates with germline specifiers.","authors":"Mami Oikawa, Hiroki Kojima, Hisato Kobayashi, Kenyu Iwatsuki, Hijiri Saito, Makoto Sanbo, Kazumi Nishioka, Tomoyuki Yamaguchi, Takuya Yamamoto, Kazuki Kurimoto, Masumi Hirabayashi, Toshihiro Kobayashi","doi":"10.1016/j.stemcr.2025.102599","DOIUrl":"10.1016/j.stemcr.2025.102599","url":null,"abstract":"<p><p>The specification of primordial germ cells (PGCs) marks a crucial branchpoint in early embryonic development. Studying the molecular mechanisms governing this process is crucial for understanding reproduction and evolution. Here, we identify transcription factors essential for PGC specification in rats using an in vitro system to induce PGC-like cells (PGCLCs) from pluripotent cells. Overexpression of Tbxt, a key mesodermal factor activating the germ cell program in epiblast-like cells, induces functional rat PGCLCs, similar to mice. However, unlike in mice, overexpression of the PGC specifiers (Prdm14, Blimp1, and Ap2γ) alone is not sufficient in rats; additional Activin and WNT signals are necessary for PGCLC induction. Through a candidate screen, we identified the transcription factor Etv4 acting cooperatively with the three PGC specifiers. Our study provides insight into the mechanism behind germline segregation in mammals and underscores the importance of using the rat model in addition to mice.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":"20 8","pages":"102599"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365847/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144849127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-08-12Epub Date: 2025-07-03DOI: 10.1016/j.stemcr.2025.102570
Emily Maguire, Jincy Winston, Sarah H Ellwood, Rachel O'Donoghue, Bethany Shaw, Atahualpa Castillo Morales, Samuel Keat, Alexandra Evans, Rachel Marshall, Lauren Luckcuck, Laura Brown, Elisa Salis, Ganna Leonenko, Nicola Denning, Nicholas D Allen, Valentina Escott-Price, Caleb Webber, Philip R Taylor, Rebecca Sims, Sally A Cowley, Julie Williams, Sarah M Carpanini, Hazel Hall-Roberts
{"title":"Modeling common Alzheimer's disease with high and low polygenic risk in human iPSC: A large-scale research resource.","authors":"Emily Maguire, Jincy Winston, Sarah H Ellwood, Rachel O'Donoghue, Bethany Shaw, Atahualpa Castillo Morales, Samuel Keat, Alexandra Evans, Rachel Marshall, Lauren Luckcuck, Laura Brown, Elisa Salis, Ganna Leonenko, Nicola Denning, Nicholas D Allen, Valentina Escott-Price, Caleb Webber, Philip R Taylor, Rebecca Sims, Sally A Cowley, Julie Williams, Sarah M Carpanini, Hazel Hall-Roberts","doi":"10.1016/j.stemcr.2025.102570","DOIUrl":"10.1016/j.stemcr.2025.102570","url":null,"abstract":"<p><p>Common forms of Alzheimer's disease (AD) are complex and polygenic. We have created a research resource that seeks to capture the extremes of polygenic risk in a collection of human induced pluripotent stem cell (iPSC) lines from over 100 donors: the IPMAR Resource (iPSC Platform to Model Alzheimer's Disease Risk). Donors were selected from a large UK cohort of 6,000+ research-diagnosed early or late-onset AD cases and elderly cognitively healthy controls, many of whom have lived through the age of risk for disease development (>85 years). We include iPSC with extremes of global AD polygenic risk (high-risk late-onset AD: 34; high-risk early-onset AD: 29; low-risk control: 27) as well as those reflecting complement pathway-specific genetic risk (high-risk AD: 9; low-risk controls: 10). All iPSC have associated clinical, longitudinal, and genetic datasets and will be available through collaboration or from cell (EBiSC) and data (DPUK) repositories.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102570"},"PeriodicalIF":5.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365843/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144565249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-07-08Epub Date: 2025-06-19DOI: 10.1016/j.stemcr.2025.102542
Jiang Xu, Alan Moreira de Araujo, Ranhui Xi, Kaihua Luo, Mingyue Han, Xiaoli Lin, Chanyi Lu, Minliang Zhou, Kurt D Hankenson, Robert F Margolskee, Ichiro Matsumoto, Guillaume de Lartigue, Myunghwan Choi, Peihua Jiang
{"title":"Gustatory-neuron-supplied R-spondin-2 is required for taste bud replenishment.","authors":"Jiang Xu, Alan Moreira de Araujo, Ranhui Xi, Kaihua Luo, Mingyue Han, Xiaoli Lin, Chanyi Lu, Minliang Zhou, Kurt D Hankenson, Robert F Margolskee, Ichiro Matsumoto, Guillaume de Lartigue, Myunghwan Choi, Peihua Jiang","doi":"10.1016/j.stemcr.2025.102542","DOIUrl":"10.1016/j.stemcr.2025.102542","url":null,"abstract":"<p><p>Replenishment of taste cells in taste buds throughout life requires innervation. Recently, we provided evidence that R-spondin is sufficient to promote taste cell generation and restore taste buds in a nerve transection model. Yet, the necessity of gustatory-neuron-supplied R-spondin 2 (RSPO2) in taste tissue homeostasis has remained unresolved. We used genetic approaches to investigate this. In a strain that carries an Rspo2 hypomorphic allele, the number of taste buds was significantly reduced in these mice, compared to wild-type mice, in both anterior and posterior tongue. Specific ablation of Rspo2 in the nodose-petrosal-jugular ganglion complex in another mouse strain led to nearly complete loss of taste buds in the circumvallate papilla. Epithelial ablation of Rnf43/Znrf3, the activity of which is antagonized by R-spondin binding, led to exuberant, sustained expansion of taste buds. Thus, our data strongly support that the RSPO2-RNF43/ZNRF3 axis serves as a master regulator for taste tissue homeostasis.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102542"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144337101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-07-08Epub Date: 2025-06-05DOI: 10.1016/j.stemcr.2025.102515
Ying Fang, Yuning Chen, Yan-Ruide Li
{"title":"Engineering the next generation of allogeneic CAR cells: iPSCs as a scalable and editable platform.","authors":"Ying Fang, Yuning Chen, Yan-Ruide Li","doi":"10.1016/j.stemcr.2025.102515","DOIUrl":"10.1016/j.stemcr.2025.102515","url":null,"abstract":"<p><p>Over the past five years, allogeneic off-the-shelf CAR-engineered cell therapies have advanced rapidly. By bypassing the individualized manufacturing, high cost, and eligibility constraints of autologous products, allogeneic platforms, especially those derived from induced pluripotent stem cells (iPSCs), promise broader, faster access for cancer patients. This perspective reviews recent preclinical and clinical milestones, outlining genetic designs, scalable production workflows, and early-phase trial outcomes. We assess safety profiles, antitumor activity, and in vivo persistence, spotlighting innovations like T cell receptor alpha constant (TRAC) knockout, human leukocyte antigen (HLA) camouflage, and interleukin (IL)-15 armoring. Finally, we identify emerging trends and challenges that will shape the future development of allogeneic iPSC-derived CAR therapies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102515"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-07-08Epub Date: 2025-06-05DOI: 10.1016/j.stemcr.2025.102512
Duo Wang, Xi Chen, Joshua Feng, Xueyuan A Jing, Jiaqi Tang, Jean Paul Chadarevian, Haeyoung Park, Matthew Lee, Fan Feng, Chao Zhang, Qi-Long Ying
{"title":"GSK3α negatively regulates GSK3β by decreasing its protein levels and enzymatic activity in mouse embryonic stem cells.","authors":"Duo Wang, Xi Chen, Joshua Feng, Xueyuan A Jing, Jiaqi Tang, Jean Paul Chadarevian, Haeyoung Park, Matthew Lee, Fan Feng, Chao Zhang, Qi-Long Ying","doi":"10.1016/j.stemcr.2025.102512","DOIUrl":"10.1016/j.stemcr.2025.102512","url":null,"abstract":"<p><p>Glycogen synthase kinase 3 (GSK3) is a crucial regulator of cellular processes, including stem cell maintenance and differentiation. Although the roles of the two GSK3 isozymes, GSK3α and GSK3β, are well documented, their specific interactions remain less understood. In this study, we explored the regulatory interplay between GSK3α and GSK3β in mouse embryonic stem cells (mESCs). Using genetic manipulation, small-molecule inhibitors, and biochemical analysis, we found that inhibition of GSK3α kinase activity increases GSK3β protein levels and activity, whereas overexpression of GSK3α reduces GSK3β protein levels and activity. Domain-swapping experiments between the two isozymes identified the glycine-rich region at the N terminus of GSK3α as the key sequence responsible for downregulating GSK3β protein levels. Our findings reveal a novel interaction between GSK3 isozymes, with GSK3α modulating GSK3β activity to maintain the balance between stem cell pluripotency and neural differentiation. This insight may open new pathways for understanding stem cell fate mechanisms and developing GSK3-targeted therapeutic strategies in regenerative medicine.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102512"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-07-08Epub Date: 2025-06-26DOI: 10.1016/j.stemcr.2025.102547
Stephanie Smith-Berdan, Mark Landon, Bryan Petkus, Leah Kramer, Alyssa Bercasio, Tuan Vo, Tobin Berger-Cahn, E Camilla Forsberg
{"title":"Vascular endothelial growth factor-induced vascular permeability results in drastic and reversible hematopoietic stem cell mobilization.","authors":"Stephanie Smith-Berdan, Mark Landon, Bryan Petkus, Leah Kramer, Alyssa Bercasio, Tuan Vo, Tobin Berger-Cahn, E Camilla Forsberg","doi":"10.1016/j.stemcr.2025.102547","DOIUrl":"10.1016/j.stemcr.2025.102547","url":null,"abstract":"<p><p>Lifelong hematopoiesis as well as hematopoietic transplantation therapies is dependent on the ability of hematopoietic stem cells (HSCs) to effectively traffic across the bone marrow (BM) endothelium. Mounting evidence suggests that modulators of vascular permeability are potent regulators of HSC location. Here, we utilized a doxycycline-inducible mouse model to overexpress vascular endothelial growth factor A (VEGF-A) to alter vascular permeability. Remarkably, VEGF-induced permeability led to unprecedented HSC mobilization. HSC mobilization from the BM to the blood stream was rapid and reversible and required no additional drugs or manipulation. The mobilized HSCs were functional, as demonstrated by high levels of long-term multi-lineage reconstitution by VEGF-mobilized cells of irradiated recipients. Importantly, VEGF-induced permeability did not irrevocably destroy vascular BM niches, as transplantation experiments revealed improved long-term donor HSC engraftment in VEGF-overexpressing recipients. Collectively, these findings enhance our ability to regulate HSC trafficking to and from the BM and provide insight into improving the efficacy and safety of HSC mobilization and hematopoietic transplantation therapies.</p>","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102547"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144512508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stem Cell ReportsPub Date : 2025-07-08Epub Date: 2025-06-04DOI: 10.1016/j.stemcr.2025.102548
Ximeng Han, Yue Wang, Wenjuan Pu, Xiuzhen Huang, Lin Qiu, Yan Li, Wei Yu, Huan Zhao, Xiuxiu Liu, Lingjuan He, Libo Zhang, Yong Ji, Jie Lu, Kathy O Lui, Bin Zhou
{"title":"Lineage Tracing Reveals the Bipotency of SOX9<sup>+</sup> Hepatocytes during Liver Regeneration.","authors":"Ximeng Han, Yue Wang, Wenjuan Pu, Xiuzhen Huang, Lin Qiu, Yan Li, Wei Yu, Huan Zhao, Xiuxiu Liu, Lingjuan He, Libo Zhang, Yong Ji, Jie Lu, Kathy O Lui, Bin Zhou","doi":"10.1016/j.stemcr.2025.102548","DOIUrl":"10.1016/j.stemcr.2025.102548","url":null,"abstract":"","PeriodicalId":21885,"journal":{"name":"Stem Cell Reports","volume":" ","pages":"102548"},"PeriodicalIF":5.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12277837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144235286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
